EFFECTS OF CHOLINERGIC MODULATION ON RESPONSES OF NEOCORTICAL NEURONSTO FLUCTUATING INPUT

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials ari sing from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varyi ng influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potas sium conductances, In particular, acetylcholine, which affects learnin g and memory, reduces the slow afterhyperpolarization, which contribut es to spike frequency adaptation. We used whole-cell patch-clamp recor dings of pyramidal neurons in neocortical slices and computational sim ulations to show, first that when fluctuating inputs were added to a c onstant current pulse, spike frequency adaptation was reduced as the a mplitude of the fluctuations was increased. High-frequency, high-ampli tude fluctuating inputs that resembled in vivo conditions exhibited on ly weak spike frequency adaptation. Second, bath application of carbac hol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input hut minimally displaced the spike tim es by < 3 ms, comparable to the spike jitter observed when a visual st imulus is repeated under in vivo conditions. These results suggest tha t cholinergic modulation may preserve information encoded in precise s pike timing, but not in interspike intervals, and that cholinergic mec hanisms other than those involving adaptation may contribute significa ntly to cholinergic modulation of learning and memory.